A continuation of our work on the stereospecific, energy-dependent transport into cultured cells addressed several issues. Glioma cells were shown to have the most active plasma membrane transport of T4 of any cells that we have examined. This was not accompanied by comparable uptake in the nuclei, suggesting a special role for thyroid hormone transport in these cells, possibly related to transcellular passage from capillary endothelium to neurons. In neuroblastoma cells, we demonstrated that plasma membrane transport of both T4 and T3 was inhibited by physiological concentrations of L-system amino acids, notably phenylalanine. A study of neuroblastoma membrane proteins by affinity labeling with bromoacetyl derivatives of thyroid hormones identified at least 2 proteins (24 kDa and 29 kDa) not previously found in other cell types. The 24 kDa protein reacted more strongly with L-T3 and the 29 kDa protein with D-T3. A novel class of thyromimetics shown to have differential effects on liver and heart in vivo was found to exert a differential effect on T3 transport into hepatoma cells and myoblasts. This may explain the effects observed in vivo.